Age changes in hepatic metabolic characteristics and their modulation by dietary manipulation

Starting at 6 weeks of age, male Fischer 344 rats were provided five different dietary regimens: group 1, fed ad libitum; group 2, restricted to 60% of the food intake of group 1; group 3, restricted to 60% of the food intake of group 1 until 6 months of age and then fed ad libitum; group 4, fed ad libitum until 6 months of age and then restricted to 60% of the food intake of group 1; group 5, given the same caloric intake as group 1 but 60% of the protein intake. The weight of the liver was maintained at about 2.5% of body weight over the wide range of body weight, age (6 through 30 months of age) and diets of this study. Liver cholesterol concentration increased with age in the rats of group 1 but not in the other groups; the hepatic cholesterol concentration was lower in the rats of groups 2 and 4 than in the others. The liver microsomal 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase activity was higher in 4-month-old rats than in rats 12 months of age and older; also, the microsomal activity from group 2 and group 4 rats was higher than that from rats of the other groups. Liver triglyceride levels increased with age in groups 1, 2, 3 and 5 but not in group 4. At all ages, postabsorptive (15 h without food) hepatic glycogen concentrations were much higher in groups 2 and 4 than in the other groups. Liver phospholipid concentration was not affected by age or diet. Basal adenylate cyclase activity in liver homogenates increased with age in all but group 4, but hormone-stimulated adenylate cyclase activity was little affected by age or diet. The age-related hepatic changes in lipids and in hormone responsiveness noted in the present study were much less marked than those previously found in blood and adipose tissue.